Development of cancer treatment by molecular targeted anti-cancer hybrid peptide against refractory cancers which are resistant to cancer chemotherapy

2013 Fiscal Year Final Research Report

• Project/Area Number: 23680089
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Clinical oncology
• Research Institution: Kyoto University
• Principal Investigator: KAWAKAMI Koji 京都大学, 医学(系)研究科(研究院), 教授 (70422318)
• Research Collaborator: HORIBE Tomohisa 京都大学, 大学院医学研究科, 特定講師 (20467468) ; KOHNO Masayuki 京都大学, 大学院医学研究科, 助教 (00437203)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 分子標的治療 / ペプチド創薬 / ハイブリッドペプチド / 難治性癌 / 治療抵抗性

Research Abstract

We focused on the targeting to transferrin receptor, IL4 receptor alpha, Neuropilin-1, and Her2 which over-express on the refractory cancer cells including pancreatic cancer and glioblastoma, and designed hybrid peptide in which targeting peptides to these receptors were conjugated with lytic type peptide that disintegrates selectively cancer cell membrane. It was found that designed hybrid peptides had effective cytotoxic and anti-tumor activities toward cancer cells over-expressing these receptors including resistant cell lines to trastuzumab and lapatinib both in vitro and in vivo. Thus, it is suggested that hybrid peptide designed in this study may provide a potent therapeutic option for patients with refractory cancer in the future.

Research Products

• [Journal Article] Immunogenicity and toxicity of transferring receptor-targeted hybrid peptide as a potent anticancer agent (2013)
  • Author(s): Kawamoto, M., Kohno, M., Horibe, T., and Kawakami, K
  • Journal Title: Cancer Chemother Pharmacol Volume: 71 Pages: 799-807
  • DOI: 10.1007/s00280-013-2074-4
• [Journal Article] Her2 targeted hybrid peptide that blocks her2 tyrosine kinase disintegrates cancer cell membrane and inhibits tumor growth in vivo (2013)
  • Author(s): Kawamoto, M., Horibe, T., Kohno, M., and Kawakami, K
  • Journal Title: Mol Cancer Ther Volume: 12 Pages: 384-393
  • DOI: 10.1158/1535-7163.MCT-12-0357
• [Journal Article] Localization of the anti-cancer peptide EGFR-lytic hybrid peptide in human pancreatic cancer BxPC-3 cells by immunocytochemistry (2013)
  • Author(s): Ohara, K., Kohno, M., and Kawakami, K
  • Journal Title: J. Peptide Sci. Volume: 19 Pages: 511-515
  • DOI: 10.1002/psc.2529
• [Journal Article] Entry of a cationic lytic-type peptide into the cytosol via endocytosis-dependent and–independent pathways in human glioma U251 cells (2013)
  • Author(s): Ohara, K., Kohno, M., Hamada, T., and Kawakami, K
  • Journal Title: Peptides Volume: 50 Pages: 28-35
  • DOI: 10.1016/j.peptides.2013.09.015
• [Journal Article] Targeting interleukin-4 receptor alpha with hybrid peptide for effective cancer therapy (2012)
  • Author(s): Yang, L., Horibe, T., Kohno, M., Haramoto, M., Ohara, K., Puri, R., and Kawakami, K
  • Journal Title: Mol Can Ther Volume: 11 Pages: 235-243
  • DOI: 10.1158/1535-7163.MCT-11-0363
• [Journal Article] A novel Transferrin-receptor-targeted hybrid peptide permeates the cancer cell membrane to induce rapid killing of cancer cells (2011)
  • Author(s): Kawamoto, M., Horibe, T., Kohno, M., and Kawakami, K
  • Journal Title: BMC cancer Volume: 11 Pages: 359
  • DOI: 10.1186/1471-2407-11-359
• [Journal Article] Semaphorin 3A-lytic hybrid peptide binding to neuropillin-1 as a novel anti-cancer agent in pancreatic cancer (2011)
  • Author(s): Ueyama, H., Horibe, T., Nakajima, O., Ohara, K., Kohno, M., and Kawakami, K
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 414 Pages: 60-66
  • DOI: 10.1016/j.bbrc.2011.09.021
• [Presentation] Novel Her2-targeted hybrid peptide that disintegrates cancer cell membrane and inhibits tumor growth in vivo (2013)
  • Author(s): Horibe, T., Kawamoto, M., Kohno, M., and Kawakami, K
  • Organizer: 第72回日本癌学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 20131003-05
• [Presentation] Confirmation of transfection efficiency for normal and cancer cell lines and monitoring of promoter activity by bioluminescence imaging at single cell level (2013)
  • Author(s): Torisawa, A., Horibe, T., Akiyoshi, R., Hatta-Ohashi, Y., Suzuki, H., and Kawakami, K
  • Organizer: 第86回日本生化学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 20130911-13
• [Presentation] Functional analysis of cytotoxic activity to glioblastoma cells by Antp-TPR hybrid peptide targeting Hsp90 (2013)
  • Author(s): Horibe, T. and Kawakami, K
  • Organizer: 第17回日本がん分子標的治療学会
  • Place of Presentation: 京都国際会館
  • Year and Date: 20130612-14
• [Presentation] 抗癌ペプチドLyticの細胞における作用機序に関する研究 (2012)
  • Author(s): 大原弘路、河野雅之、川上浩司
  • Organizer: 第49回ペプチド討論会
  • Place of Presentation: 鹿児島県民交流センター
  • Year and Date: 20121107-09
• [Presentation] Anti-leukemic activity of hybrid Antp-TPR peptide targeting Hsp90 (2011)
  • Author(s): Horibe, T., Kawamoto, M., Kohno, M., and Kawakami, K
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 20111003-05
• [Presentation] Enhancement of anticancer activity by the single amino acid conversion of EGFR-binding peptide (2011)
  • Author(s): Tada, N., Horibe, T., Haramoto, M., Ohara, K., Kohno, M., and Kawakami, K
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都国際会館
  • Year and Date: 20110921-24
• [Presentation] Mechanism of cancer cell death by hybrid Antp-TPR peptide targeting Hsp90 (2011)
  • Author(s): Horibe, T., Kohno, M., Haramoto, M., Ohara, K., and Kawakami, K
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都国際会館
  • Year and Date: 20110921-24
• [Remarks] 研究室ホームページ
  • URL: http://square.umin.ac.jp/kupe/